CREB is activated by muscle injury and promotes muscle regeneration.
CREB is activated by muscle injury and promotes muscle regeneration.
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DOI：
10.1371/journal.pone.0024714
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Berdeaux R
中科院分区：
文献类型：
--
作者：
Stewart R;Flechner L;Montminy M;Berdeaux R
cAMP反应元件结合蛋白（CREB）在胚胎骨骼肌祖细胞的分化和成体骨骼肌的存活中起着关键作用。然而，很少有人知道的生理信号，激活CREB在正常肌肉。在这里，我们表明，CREB磷酸化和靶基因诱导急性肌肉损伤后和再生过程中，由于基因突变。激活的CREB定位于肌源性前体细胞和再生区域内的新再生肌纤维。此外，我们发现来自受损骨骼肌组织的信号诱导CREB磷酸化和小鼠原代成肌细胞中靶基因的表达。活化的CREB突变体（CREBY 134 F）增强成肌细胞增殖以及培养的原代肌细胞中早期肌源性转录因子的表达。一致地，激活的CREB-YF促进体内急性肌肉损伤后的成肌细胞增殖，并增强营养不良mdx小鼠的肌肉再生。我们的研究结果揭示了CREB在促进骨骼肌再生中的一种新的生理功能。
The cAMP response element binding protein (CREB) plays key roles in differentiation of embryonic skeletal muscle progenitors and survival of adult skeletal muscle. However, little is known about the physiologic signals that activate CREB in normal muscle. Here we show that CREB phosphorylation and target genes are induced after acute muscle injury and during regeneration due to genetic mutation. Activated CREB localizes to both myogenic precursor cells and newly regenerating myofibers within regenerating areas. Moreover, we found that signals from damaged skeletal muscle tissue induce CREB phosphorylation and target gene expression in primary mouse myoblasts. An activated CREB mutant (CREBY134F) potentiates myoblast proliferation as well as expression of early myogenic transcription factors in cultured primary myocytes. Consistently, activated CREB-YF promotes myoblast proliferation after acute muscle injury in vivo and enhances muscle regeneration in dystrophic mdx mice. Our findings reveal a new physiologic function for CREB in contributing to skeletal muscle regeneration.
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